Apparatus For Treating Age-Related Macular Degeneration (ARMD)

ABSTRACT

Apparatus for treating age-related macular degeneration, the apparatus comprising a light source which, in operation, serves to emit a therapeutic light beam presenting an emission wavelength lying in the range 1.2 μm to 1.3 μm, and preferably equal to 1.26 μm to 1.27 μm. The laser source preferably comprises an optical fiber Raman laser.

The present invention relates to an apparatus used in opthalmology fortreating age-related macular degeneration (ARMD), and more particularlyARMD of the exudative type, by means of a light beam, and moreparticularly by means of a “non-thermal” laser.

BACKGROUND OF THE INVENTION

Age-related macular degeneration (ARMD) constitutes a severe threat tovision, and the frequency of cases of ARMD is tending to increasebecause of lengthening lifetimes and various environmental factors anddaily exposure to light, which factors are also combined with geneticpredispositions.

ARMD results in a progressive loss of macular vision cells. It is themajor cause of poor vision in industrialized countries for people agedmore than fifty, but it affects the macula only. It therefore cannotlead to complete blindness.

There are two main forms of ARMD:

Dry or atrophic ARMD which is characterized by the formation of smallspots or “drusen” under the retina and by atrophy of the retinalpigmentary epithelium. There exists no treatment for this type of ARMD,in particular by means of a laser.

Wet or exudative ARMD is characterized by the presence of abnormal bloodvessels or neovascularization. These vessels are fragile, can bleed,leak, develop, and progressively destroy the macula. As a general rule,in order to be able to see them, it is necessary to perform angiographywhich displays them accurately. Angiography using fluorescein revealsfluid leaks and retinal neovascularization, while angiography usingindocyanine green reveals choroidal and occult new vessels. Angiographyconsists in injecting dye into the veins in order to observe retinal andchoroidal blood vessels better and in order to photograph the retinaafter various lengths of time have elapsed.

The first signs of the disease can be seen only by an ophthalmologist,and they are detected by examining the back of the eye, and possiblyalso by performing angiography with fluorescein or indocyanine green.The patient perceives symptoms only once the disease has already reachedan advanced stage. There is no pain.

The most common symptom is a loss of visual acuity: initially in theform of a need for increased light levels when reading. Fewer detailscan be seen and certain features of the face disappear or certainletters or words in a phrase disappear when reading. Another symptom isalarming and makes people consult quickly: this is the appearance ofstraight lines that become deformed.

At a more advanced stage, central vision is highly degraded (a blackspot in the center of the field of vision): faces are no longerrecognized, and reading and writing become impossible. Peripheral visionis conserved and allows the patient to be mobile and remain independent.

Various treatments are made available to patients suffering from ARMD.Therapeutic indications cannot be described in greater detail insofar asnumerous treatments are presently under evaluation. In addition, none ofthose treatments enables ARMD to be cured. It is possible only to haltdegeneration or to slow down the advance of the disease.

There are thermal-type treatments in which a heating effect islooked-for and used, and there are other treatments.

The two thermal-type treatments are photocoagulation by laser treatmentand thermal therapy through the pupil.

Photocoagulation by Laser Treatment

This is the first treatment to have demonstrated effectiveness on aclinical form of new vessels; visible neovascularization outside orbeside the fovea.

This treatment is difficult to perform. The purpose of the treatment isto burn the new vessels by releasing a high temperature in the vicinitythereof. More precisely, the coherent laser beam interacts with the backportion of the retina (the pigmentary epithelium) which absorbs light.This reaction raises the temperature at the back of the epithelium,thereby also leading in harmful manner to definitive lesions in thephotodetectors.

Transpupillary Thermal Therapy (TTT)

Transpupillary thermal therapy is treatment that consists in using alaser to heat the zone for treatment as in laser photocoagulationtreatment. However, in this treatment, the laser beam is used to raisetemperature to a smaller extent than with conventional photocoagulationtreatment. This is in an attempt to avoid the above-mentioned lesionsdue to using a laser that gives off high temperatures. Nevertheless, inorder to obtain a therapeutic effect while heating less strongly, it isnecessary to apply the laser beam for a longer duration (several tens ofseconds). This is described in international patent application WO02/45633. In particular, the recommended duration of irradiation forthis treatment lies in the range 30 seconds (s) to 40 s. Unfortunately,any laser treatment is precision treatment that requires the zone fortreatment to remain stationary throughout the duration of the treatment.Keeping a patient's eye stationary for several tens of seconds is notpossible, unless the treatment is applied under anesthesia.

There are also two non-thermal type treatments constituted byconventional medication and dynamic phototherapy.

Medication Treatments

At present, no treatment by medication has been successful. Thetreatments that have been studied the most are those relying onsupplying additional oligo-elements and vitamins: vitamins A and E,selenium, zinc, . . . . The idea is to cause the retina to operate underbetter metabolic conditions and thus limit the risk of accumulating thewaste associated with aging.

Dynamic Phototherapy (OPT)

Dynamic phototherapy is a recent method which consists in combining aphotosensitive drug with a “non-thermal” laser (one that does not burnthe retina), in contrast to the lasers used for photocoagulation.

The photosensitive drug, such as that sold under the trademarkVisudyne®, for example, is injected intravenously into the body of thepatient. This drug rapidly reaches the abnormal blood vessels of theretina where it becomes fixed to the inside walls of these new vessels.Thereafter, the portion of the macula that is to be treated isilluminated with a red laser, e.g. at a wavelength of 689 nanometers(nm), and for a duration of 90 s. The laser beam serves to activate thephotosensitive drug which leads to a sequence of chemical reactionstaking place inside the new vessels, causing the abnormal vessels in theretina to become occluded, and subsequently to disappear. Moreparticularly, the action of the laser beam on the molecules of thephotosensitive substance serves mainly to generate singlet oxygen (¹O₂),which is the main agent serving to occlude abnormal retinal vessels.

The latest studies have given results that are very satisfactory, with60% of patients treated presenting visual acuity that is stabilized orimproved. Nevertheless, that method presents several drawbacks. Thefirst drawback is associated with patients being photosensitized, whichobliges them to avoid any exposure to the sun for a relatively longperiod of time, generally of the order of 48 hours (h). Another drawbackis associated with injecting a drug (a photosensitive substance) that isexpensive, thus making the treatment expensive, it being understood thatthe treatment needs to be repeated in order to be effective. Finally,with some patients, injecting a photosensitive drug can lead to sideeffects that are harmful.

OBJECTS AND SUMMARY OF THE INVENTION

An object of the present invention is thus to provide a method andapparatus for treating ARMD, and in particular wet ARMD, which, in amanner comparable with dynamic phototherapy, make use of a therapeuticlight beam that is non-thermal and non-destructive (unlike the laserused for photocoagulation or in transpupillary thermal therapy), butwhich do not require a photosensitive drug to be injected.

The technique of the invention relies on using a laser source thatpresents an emission wavelength lying in the range 1.2 micrometers (μm)to 1.3 μm, and preferably in the range 1.26 μm to 1.27 μm.

The invention thus provides apparatus for laser treatment of age-relatedmacular degeneration, which apparatus includes, in known manner, a lightsource that, in operation, serves to emit a non-thermal therapeuticlight beam.

In a manner characteristic of the invention, said light source isdesigned to emit a non-thermal therapeutic light beam presenting anemission wavelength lying in the range 1.2 μm to 1.3 μm, and preferablyin the range 1.26 μm to 1.27 μm, so as to lie in the wavelength rangethat corresponds specifically to the molecular transition of oxygen,thus enabling intracellular singlet oxygen to be generated directly andin sufficient quantity.

The invention also provides a method of treating age-related maculardegeneration consisting in illuminating the macula with a non-thermaltherapeutic light beam presenting an emission wavelength lying in therange 1.2 μm to 1.3 μm, and preferably in the range 1.26 μm to 1.27 μm,so as to lie in a wavelength range corresponding specifically to themolecular transition of oxygen, thus enabling intracellular singletoxygen to be generated directly and in sufficient quantity.

The light source is preferably a laser source producing a coherenttherapeutic light beam.

Preferably, but in a manner that is not limiting for the invention, thelaser source used is an optical fiber Raman laser.

More particularly, the power of the laser source lies in the range 1milliwatt (mW) to 1 watt (W), and preferably lies in the range 10 mW to1 W.

It has been found that using a therapeutic light beam at theabove-specified particular frequencies makes it possible advantageouslyand in surprising manner to obtain results that are satisfactory whentreating ARMD (retarding the loss of visual acuity, and possibly evenimproving visual acuity), without it being necessary to use a drug. Aposteriori, it seems plausible that the action of the therapeutic lightbeam in the above-specified wavelength range serves to generate singletoxygen directly from the blood contained in the new vessels, and does soin sufficient quantity to obtain therapeutic effects that are comparableto those obtained after injecting a photosensitive drug. Thus, unlikethe above-mentioned DPT method, the light beam no longer acts on anintermediate substance (the photosensitive drug) in order to generatesinglet oxygen, but given the above-mentioned particular wavelengthrange of the light beam used in the invention, said beam acts directlyon the oxygen contained in the new vessels in order to generate singletoxygen. Nevertheless, the Applicant is not tied to this explanation.

BRIEF DESCRIPTION OF THE DRAWINGS

Other characteristics and advantages of the invention appear moreclearly in the light of the following description of a preferredembodiment of treatment apparatus of the invention and of its method ofuse, which description is given by way of non-limiting example and withreference to the accompanying drawings, in which:

FIG. 1 shows an example of treatment apparatus of the invention of thetype having a slit-lamp;

FIG. 2 is a diagram showing the two main light sources (the therapeuticsource and the illumination source) mounted inside the treatment unit ofthe FIG. 1 apparatus; and

FIG. 3 is a diagram of an optical fiber Raman laser implemented in theFIG. 1 apparatus.

MORE DETAILED DESCRIPTION

FIG. 1 shows an embodiment of apparatus of the invention for treatingARMD, which apparatus is of the slit-lamp type.

In the usual manner for slit-lamps, this apparatus essentiallycomprises:

-   -   an optical unit 1 enabling a practitioner to observe the eye        being treated;    -   a treatment unit 2 serving to generate a light beam 3, which        beam is directed vertically on leaving the treatment unit 2, in        the present example;    -   a mirror 4 for deflecting the light beam 3 through 90° so that        it propagates horizontally on the same optical axis as the        optical observation axis of the optical unit 2; and    -   means 5 of the chin-rest type for positioning the patient's head        relative to the optical unit 1 and the light beam 3, and thus        positioning the eye that is to be treated.

With reference to FIG. 2, the treatment unit 2 comprises a therapeuticlight source 20 and a conventional light source 22 for illuminating theeye (standard illumination lamp). The therapeutic light beam 20 a comingfrom the source 20 is coupled in conventional manner with theilluminating beam 22 a coming from the light source 22 by means of anoptical coupling system 23, after being shaped in conventional manner(using an optical collimator system 21). In operation, theabove-mentioned light beam 3 is emitted from the outlet of the treatmentunit 2, which beam corresponds both to the therapeutic light beam and toa non-therapeutic light beam enabling the eye to be illuminated so thatthe eye can be observed by means of the optical unit 1.

The invention lies in the light source 20 of the unit 2, which lightsource is described in greater detail below. The other elements of theapparatus are those that are usually implemented in prior artslit-lamps, so they are not described in greater detail below.

In the general manner of the invention, the light source 20 is designedto emit a therapeutic light beam 20 a presenting an emission wavelengthlying in the range 1.2 μm to 1.3 μm.

The therapeutic light beam 20 a is preferably a coherent light beam(laser). Nevertheless, in another embodiment, the therapeutic light beam20 a could be a non-coherent light beam generated by a light source ofsufficient power followed by optical filtering so as to retain onlythose frequency components that lie in the range 1.2 μm to 1.3 μm.

When the beam 20 a comprises coherent light, the most general definitionof the invention is not limited to any particular type of laser source20, and any laser source that is suitable for emitting a laser beamsatisfying the above-specified wavelength condition and known to theperson skilled in the art could be used. In particular, and innon-exhaustive manner, it is possible to use laser sources of thefollowing types:

-   -   a continuous or pulsed optical fiber Raman laser;    -   a continuous or pulsed Cr:Forsterite (Cr₄+:Mg₂SiO₄) laser        optically pumped by a neodymium-doped (Nd-doped) optical fiber        or solid laser, by an ytterbium-doped (Yb-doped) optical fiber        or solid laser, or by a diode;    -   a continuous or pulsed parametric oscillator, pumped by another        laser source;    -   a laser diode; or    -   a continuous or pulsed solid Raman converter or laser pumped by        another laser source.

Amongst the above lasers, it is preferable to use an optical fiber Ramanlaser, mainly for the following reasons:

-   -   the fiber outlet from the laser makes it easier to convey the        beam to the outlet of the treatment unit 2;    -   the laser beam 20 a that is generated thereby presents good        spatial and spectral quality;    -   in advantageous manner, the laser source 20 is compact;    -   the laser source 20 is reliable and does not require any        maintenance; and    -   this type of laser source provides the best compromise between        quality and manufacturing cost of the laser.

Preferred Embodiment of an Optical Fiber Raman Laser Having a WavelengthLying in the Range 1.2 μm to 1.3 μm (FIG. 3)

The laser source 20 used in the treatment unit 2 is preferably anoptical fiber Raman laser designed to emit a therapeutic laser beam 20 aat a wavelength in the range 1.26 μm to 1.27 μm, and at a power levellying in the range 1 mW to 1 W, and preferably in the range 10 mW to 1W.

With reference to FIG. 3, the optical fiber Raman laser comprises apumped laser diode 201 at a wavelength of 910 nm to 930 nm or 970 nm to980 nm, an ytterbium-doped optical fiber laser 202, and a Ramanconverter 204 serving to transpose the wavelength of the beam beingoutput by the optical fiber laser 202 so as to obtain a laser beamhaving a wavelength in the range 1260 nm to 1270 nm.

The Yb-doped optical fiber laser 202 is constituted by a dual-cladoptical fiber 205 with an ytterbium-doped core and two Bragg gratings207 a, one at its inlet and another at its outlet, which gratings arephoto-inscribed in the fiber. The outlet 203 of the Yb laser fiber 202is welded directly to the inlet of the Raman converter 204.

The Raman converter 204 comprises an optical fiber 206 with aphosphorous-doped core and two Bragg gratings 207 b, one at its inletand the other at its outlet, which gratings are adjusted to a wavelengthin the range 1260 nm to 1270 nm. This converter serves to transpose theemission wavelength of the Yb laser 202 in a single step.

In another variant, it is possible to use a monomode or a multimodeoptical fiber different from the fiber described above; under suchcircumstances, the number of conversion steps performed by the Ramanconverter 204 needs to be adapted as a function of the nature of thefiber, and in particular of the dopant used.

It is also possible to replace the Bragg gratings by monomode couplers.

Power is controlled by means of a coupler 208 presenting a low couplingratio, and a photodiode 209 connected to control electronics 210,serving to control the outlet power 215, e.g. by acting directly on thecurrent fed to the pump diode 201. The control electronics 210 enablesthe practitioner to adjust the power of the therapeutic laser beam 20 amanually over the range 1 mW to 1 W, and preferably over the range 10 mWto 1 W.

By way of example, the outlet 215 of the optical fiber Raman laser isfitted with an outlet connector (not shown in the figures, butconstituted by an FC, SMA, etc. type connector) serving to enable it tobe connected easily and directly to the collimator optical system 21 ofthe slit-lamp.

An actuation pedal 211 or equivalent means connected to the controlelectronics 210 is also provided to enable the practitioner to controltriggering of the therapeutic laser beam 20 a.

According to an additional characteristic, the laser source 20 alsoincludes aiming means 212, 213, and 214. More particularly, these aimingmeans comprise a red optical fiber laser diode 212 which emits in thewavelength range 630 nm to 690 nm and which is coupled to the outlet ofthe optical fiber Raman laser via an attenuator 213 and a monomodewavelength-division multiplex (WDM) coupler 214. The diode 212 serves asan aiming source and enables the practitioner (via the optical unit 1)to view the point of impact of the therapeutic laser beam.

The optical fiber Raman laser described above with reference to FIG. 3and serving to emit a therapeutic laser beam at a wavelength lying inthe range 1.2 μm to 1.3 μm is novel in itself, and can thusadvantageously also be used in other applications, whether medical ornon medical, and outside the particular field of treating ARMD.

The apparatus of the invention is implemented as follows. The patientplaces his/her head on the chin rest 5. The practitioner adjusts thethree-dimensional position of the eye that is to be treated relative tothe beam 3 in very accurate, but conventional, manner by visualizing theimpact of the therapeutic laser beam 20 a by means of the aiming beamthat is produced continuously by the diode 212. Once alignment is exact,the practitioner adjusts the emission power of the therapeutic laser 20a and actuates the control pedal or equivalent 211 for a predeterminedlength of time, thereby causing the therapeutic laser beam to be emitted(to illuminate the zone of the macula that is to be treated). Theduration of the treatment is determined by the practitioner. Electronicmeans for controlling this treatment duration may optionally be providedin the apparatus. Once the target zone of the macula has been treated,the practitioner repeats the same operations on a new diseased zone (theeye being newly aligned relative to the beam 3).

1. Apparatus for treating age-related macular degeneration, theapparatus comprising a light source which, in operation, enables atherapeutic light beam to be emitted in a manner similar to the lightsource used in the context of dynamic phototherapy, wherein said lightsource is designed to emit a therapeutic light beam presenting anemission wavelength lying in the range 1.26 μm to 1.27 μm, therebygenerating intracellular singlet oxygen directly and in sufficientquantity.
 2. Apparatus according to claim 1, wherein the power of thetherapeutic light beam lies in the range 1 mW to 1 W, and preferably inthe range 10 mW to 1 W.
 3. Apparatus according to claim 1, wherein thetherapeutic light source is a laser source.
 4. Apparatus according toclaim 3, wherein the laser source comprises an optical fiber Ramanlaser.
 5. Apparatus according to claim 4, wherein the optical fiberRaman laser comprises a pump laser diode, an ytterbium-doped opticalfiber laser, and a Raman converter serving to transpose the wavelengthof the beam coming from the ytterbium-doped optical fiber laser. 6-10.(canceled)